Figure 1.

UPF3B mutations identified in this study. cDNA (NM_080632) and protein (NP_542199) annotation of individual mutations is shown for each family. (a) Family 1 (previously reported)²⁹. A four-nucleotide deletion, 674_677delGAAA, has been identified in this family; it was present in the two affected brothers and their mother (II-2; 100% X-chromosome inactivation skewing) but was absent in the grandmother (I-2; random, 61:39 skewing), indicating a probable de novo mutation event in the mother (II-2). (b) Family 2 (ascertained in Australia). The mutation was present in both affected boys and the mother. (c) Family 3, from the UK. Three generations with affected males have been recorded. This mutation, which causes a PTC, was identified in four affected males (no sample was available from II-3) and three obligate female carrier mothers (II-1, III-1 and III-3) and was absent from three unaffected males (II-5, III-4 and IV-2). (d) Family 4 (two generations of affected males; from the USA). The X chromosome inactivation assay showed moderately to highly skewed inactivation in all carrier females in this family, whereas noncarriers showed random skewing (data not shown; see also Methods). Open symbols represent normal individuals, and filled squares represent affected males. Probands in each family are indicated with arrows. Individual generations are numbered with Roman numerals (I, II, III). WT, wild-type allele; MUT, mutant allele; NT, not tested. DNA sequence chromatograms of individual mutations and wild-type alleles are given in Supplementary Figure 1 online.